Bioanalysis最新文献

{"title":"Novel assay format for total anti-adeno-associated virus antibody detection with low capsid consumption and built-in specificity control.","authors":"Uwe Wessels, Florian Neff, Julia Fakhiri, Klaus Mayer, Ulrich Brinkmann, Kay Stubenrauch","doi":"10.4155/bio-2023-0254","DOIUrl":"10.4155/bio-2023-0254","url":null,"abstract":"<p><p><b>Aim:</b> To develop an assay format for detection of total anti-adeno-associated virus 2 (AAV2) antibodies with low capsid material consumption. <b>Methods:</b> An immune complex (IC) assay format was developed. The format is based on the formation of ICs in solution and their subsequent detection using an anti-AAV2 antibody for capture and an antibody against the study species IgG for detection. <b>Results:</b> The feasibility of the IC assay for detection of preexisting and treatment-emergent anti-AAV2 antibodies was demonstrated in cynomolgus monkey and human serum samples, including samples from a preclinical study with AAV2-based therapies. <b>Conclusion:</b> The presented IC assay is an easy-to-perform total anti-AAV2 antibody assay that requires a small amount of unlabeled capsid material and provides an intrinsic specificity control.</p>","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolite identification and quantitation of RBD1016 siRNA: a direct comparison of hybridization-based LC-FD and LC-HRAM assays.","authors":"Yuhuan Ji, Zhaoxu Guo, Min Yan, Limin Chu, Min Meng, Yantao Chu, Hong Yu, Laixin Wang","doi":"10.4155/bio-2023-0161","DOIUrl":"10.4155/bio-2023-0161","url":null,"abstract":"<p><p><b>Aim:</b> RBD1016 is an <i>N</i>-acetylgalactosamine-conjugated siRNA drug currently in a phase II trial for treatment of chronic hepatitis B virus. To evaluate its absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic/pharmacodynamic (PK/PD) properties, two LC-based bioanalytical methods, LC-high-resolution/accuracy MS and LC-fluorescence detection, were developed and qualified. <b>Materials & methods:</b> The LC-high-resolution/accuracy MS method was used for metabolite identification and simultaneous quantitation of the antisense and sense strands as well as their respective metabolites. The LC-fluorescence detection assay was primarily used for analyzing the antisense strand and its metabolites in low-concentration plasma samples. The two methods were successfully bridged by analyzing the same sets of study samples. <b>Results & conclusion:</b> Both methods were found to have excellent accuracy/precision, specificity and reproducibility to support ADME and PK/PD studies of RBD1016 siRNA.</p>","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2023 White Paper on Recent Issues in Bioanalysis: Deuterated Drugs; LNP; Tumor/FFPE Biopsy; Targeted Proteomics; Small Molecule Covalent Inhibitors; Chiral Bioanalysis; Remote Regulatory Assessments; Sample Reconciliation/Chain of Custody <u>(PART 1A</u> - Recommendations on Mass Spectrometry, Chromatography, Sample Preparation Latest Developments, Challenges, and Solutions and BMV/Regulated Bioanalysis <u>PART 1B</u> - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV, Biomarkers/IVD/CDx/BAV, Immunogenicity, Gene & Cell Therapy and Vaccine).","authors":"Mike Baratta, Wenying Jian, Shawna Hengel, Surinder Kaur, Jennifer Cunliffe, Jason Boer, Nicki Hughes, Sumit Kar, John Kellie, Yeoun Jin Kim, Michael Lassman, John Mehl, Ling Morgan, Joe Palandra, Hetal Sarvaiya, Jianing Zeng, Naiyu Zheng, Jian Wang, Long Yuan, Allena Ji, Christopher Kochansky, Lin Tao, Yue Huang, Estelle Maes, Luca Barbero, Kevin Contrepois, Luca Ferrari, Yunlin Fu, Jay Johnson, Barry Jones, Monika Kansal, Yang Lu, Noah Post, Honglue Holly Shen, Yongjun Y-J Xue, Yiyue Cynthia Zhang, Gopa Biswas, Seongeun Julia Cho, Anna Edmison, Kimberly Benson, Lee Abberley, Mitra Azadeh, Jennifer Francis, Fabio Garofolo, Shalini Gupta, Iordanka Dany Ivanova, Akiko Ishii-Watabe, Shane Karnik, Sean Kassim, Olga Kavetska, Steve Keller, Elham Kossary, Wenkui Li, Fred McCush, Dulcyane Neiva Mendes, Mohsen Rajabi Abhari, Kara Scheibner, Timothy Sikorski, Roland F Staack, Edward Tabler, Huaping Tang, Katty Wan, Yow-Ming Wang, Emma Whale, Li Yang, Jennifer Zimmer, Abbas Bandukwala, Xiulian Du, Olga Kholmanskikh, Sonja Kwadijk-de Gijsel, Meenu Wadhwa, Joshua Xu, Alessandra Buoninfante, Isabelle Cludts, Sandra Diebold, Kimberly Maxfield, Christian Mayer, Joao Pedras-Vasconcelos, Mohsen Rajabi Abhari, Sophie Shubow, Yoichi Tanaka, Omar Tounekti, Daniela Verthelyi, Leslie Wagner","doi":"10.1080/17576180.2024.2347153","DOIUrl":"10.1080/17576180.2024.2347153","url":null,"abstract":"<p><p>The 17^th Workshop on Recent Issues in Bioanalysis (17^th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17^th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on \"EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with this NEW Regulation\" and on \"US FDA/OSIS Remote Regulatory Assessments (RRAs)\" were the special features of the 17^th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication covers the recommendations on Mass Spectrometry Assays, Regulated Bioanalysis/BMV (Part 1A) and Regulatory Inputs (Part 1B). Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 7 and 8 (2024), respectively.</p>","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Internal standard variability: root cause investigation, parallelism for evaluating trackability and practical considerations.","authors":"Jinhui Zhang, Arindam Dasgupta, Ruben Ayala, Charles Bonapace, Sean Kassim, Patrick J Faustino","doi":"10.1080/17576180.2024.2348939","DOIUrl":"10.1080/17576180.2024.2348939","url":null,"abstract":"","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unique challenges required reassessment and alterations to critical reagents to rescue a neutralizing antibody assay.","authors":"Blake A Rowe, Katie Medina-Carle, Keguan Chen, Kimberly J Reese, Kenneth M McCarthy, Amy A Concannon, George R Gunn, Andrew P Gehman, Yong Jiang, Erik Meyer","doi":"10.1080/17576180.2024.2360363","DOIUrl":"10.1080/17576180.2024.2360363","url":null,"abstract":"<p><p><b>Aim:</b> To redevelop a neutralizing antibody (NAb) assay to be much more drug tolerant, have a large dynamic range and have high inhibition when using high levels of positive control (PC).<b>Materials & methods:</b> Early assay data suggested that typical biotin labeling of the capture reagent (Drug 1, produced in a human cell line) was blocking it from binding with the PC or the detection target, and that the detection target was out competing the PC. Methodical biotin labeling experiments were performed at several challenge ratios and an Fc linker was added to the detection target.<b>Results & conclusion:</b> A larger dynamic range, high inhibition and higher drug tolerance were achieved by adding an acid dissociation step to the assay, performing atypical biotin labeling of Drug 1 and switching to a detection target that contained an Fc linker to increase steric hinderance and decrease its binding affinity to Drug 1.</p>","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hybrid IA-LC-MS/MS method for adrenocorticotropic hormone(1-24) to support interpretation of low-dose cosyntropin-stimulation test.","authors":"Barry R Jones, Junlong Shao, Mitesh Sanghvi, Alejandro Ayala, Rosa Luo, Jian Wang","doi":"10.1080/17576180.2024.2360358","DOIUrl":"10.1080/17576180.2024.2360358","url":null,"abstract":"<p><p>Adrenocorticotropic hormone 1-24 (ACTH[1-24]) has a similar effect as endogenous ACTH(1-39) to generate cortisol by targeting the MC2R receptor on the adrenal gland. A new investigational ACTH receptor antagonist drug is being developed to treat diseases of ACTH excess (e.g., Cushing's disease) by binding to the MC2R receptor. Administration of ACTH(1-24) was used in a Phase I clinical study to assess the ability of this drug candidate to suppress the cortisol response to ACTH stimulation. A hybrid immunoaffinity-LCMS assay measuring ACTH(1-24) with a concentration range of 10 to 400 pg/ml was developed to support the study. Consistent and acceptable A&P results were achieved. The assay development and qualification will be discussed.</p>","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodistribution of lipid nanoparticle, eGFP mRNA and translated protein following subcutaneous administration in mouse.","authors":"Åsa Sandelius, Humaira Naseer, Johnny Lindqvist, Amanda Wilson, Neil Henderson","doi":"10.1080/17576180.2024.2360361","DOIUrl":"10.1080/17576180.2024.2360361","url":null,"abstract":"<p><p><b>Aim:</b> Increased knowledge of biodistribution and pharmacokinetics of lipid nanoparticle (LNP)-encapsulated mRNA drug components may aid efficacy and safety evaluation.<b>Methods:</b> Mice were subcutaneously administrated LNP encapsulated enhanced green fluorescent protein mRNA and sampled up to 72 h after dosing. LNP, mRNA and translated protein were quantified by LC-MS, branched DNA and ELISA.<b>Results:</b> Highest levels of LNP and mRNA were detected in skin, followed by spleen, but also rapidly distributed to circulation. Translated protein showed high concentration in skin and spleen, but also in liver and kidney across 24 h where the LNP was cleared at 4 h.<b>Conclusion:</b> Subcutaneously dosing LNP encapsulated mRNA in mice resulted in a nonlinear relationship of LNP, mRNA and protein concentration across multiple tissues.</p>","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioanalysis of free antisense oligonucleotide payload from antibody-oligonucleotide conjugate by hybridization LC-MS/MS.","authors":"Di Jiang, Pei Li, Long Yuan","doi":"10.1080/17576180.2024.2368339","DOIUrl":"10.1080/17576180.2024.2368339","url":null,"abstract":"<p><p><b>Background:</b> Antisense oligonucleotides (ASOs) have been conjugated to various moieties, such as peptides, antibodies or Fab regions of antibodies, to enhance their delivery to target tissues. The quantitation of free ASO (ASO payload) is critical to characterize its pharmacokinetics/pharmacodynamics (PK/PD) properties and biodistribution after delivery of the peptide/antibody/Fab ASO conjugates.<b>Results:</b> We developed a hybridization-based LC-MS/MS methodology for quantification of free ASO in tissues in the presence of Fab-ASO and ASO with linker (ASO-linker).<b>Conclusion:</b> The developed method was applied to measure accurately the free ASO concentrations in liver and gastrocnemius in mice that were dosed with Fab-ASO. This methodology has also been applied to free ASO bioanalysis for other antibody-ASO and Fab-ASO conjugates in various tissues and plasma/serum samples.</p>","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The case for bioanalytical analyzer.","authors":"Ming Li","doi":"10.1080/17576180.2024.2344328","DOIUrl":"10.1080/17576180.2024.2344328","url":null,"abstract":"","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-MS/MS-based bioanalysis of branched-chain and aromatic amino acids in human serum.","authors":"Tianyi Wang, Yalian Zhang, Luan Jia, Ying Li, Lu Wang, Yanru Zhu, Yuxin Jiang, Furong Zhao, Shuang Wang, Dan Song","doi":"10.1080/17576180.2024.2387467","DOIUrl":"10.1080/17576180.2024.2387467","url":null,"abstract":"<p><p><b>Aim:</b> Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were suggested as potential biomarkers in liver disease. This study aimed to develop and validate a simple and rapid LC-MS/MS method to simultaneously measure serum BCAAs and AAAs levels in patients with liver injury, and further establish reference intervals of Chinese healthy adult populations.<b>Patients & methods:</b> Samples were prepared by a one-step protein precipitation and analysis time was 4 min per run.<b>Results:</b> The validation results showed good linearity (r² >0.9969), satisfactory accuracy (94.44% - 107.75%) and precision (0.10% - 5.90%).<b>Conclusion:</b> This method proved to be suitable for high-throughput routine clinical use and could be a valuable adjunct diagnosis tool for liver injury and other clinical applications.</p>","PeriodicalId":8797,"journal":{"name":"Bioanalysis","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}